HCV New Drugs

Current treatment recommendations in HCV liver transplant recipients

Hello everyone, today I hope to offer a bit of information to all those brave people waiting for a liver transplant. You may wish to either file the information away for future reference or pass it along.  

We start with a review article about treating cirrhosis, recurrent HCV, or treating HCV after liver transplantation.

The Research

Review
Published on Nov 7 2016; World J Gastroenterol
Concise review: Interferon-free treatment of hepatitis C virus-associated cirrhosis and liver graft infection
This concise review gives an overview about most current prospective trials and cohort analyses for treatment of patients with liver cirrhosis and liver graft recipients. In patients with compensated cirrhosis Child-Pugh-Turcotte (CTP) class A, all approved agents are safe and SVR rates do not significantly differ from patients without cirrhosis in general. In patients with decompensated cirrhosis CTP class B or C, daclastasvir, ledipasvir, velpatasvir, and sofosbuvir are approved, and SVR rates higher than 90% can be achieved. Especially for patients with a model of end stage liver disease score higher than 15 and therefore eligible for liver transplantation, data is scarce. Reported SVR rates in patients with cirrhosis CTP class C are lower compared to patients with a less severe liver disease. In liver transplant recipients with a maximum of CTP class A, SVR rates are comparable to patients without LT. Patients with decompensated graft cirrhosis should be treated on an individual basis.

In the May issue of Current Opinion in Gastroenterology, Paul Y Kwo, M.D., reported on five effective all oral  therapies for patients who develop recurrent HCV after liver transplantation; Sovaldi, Harvoni, Daklinza, Olysio, and Viekira Pak.     

The article is available online for free over at Medscape, here is a summary:

Recent findings: The introduction of direct acting antiviral agents to posttransplant patients has demonstrated that sustained virologic response rates that are comparable with nontransplant patients can be achieved with excellent tolerability. The combinations of (Sovaldi) sofosbuvir/ribavirin, (Harvoni) ledipasvir/sofosbuvir/ribavirin, (Daklinza) daclatasvir/sofosbuvir/ribavirin, sofosbuvir/ (Olysio) simeprevir /- ribavirin, and (Viekira Pak) paritaprevir/ombitasvir/dasabuvir/ribavirin have all achieved high sustained response rates posttransplants. The previously dreaded complication of fibrosing cholestatic hepatitis C can now be effectively treated.

Summary:

All of the AASLD/IDSA recommended regimens for post-transplant treatment of HCV are interferon-free regimens. For a summary of the recommendations see the summary boxes, or read the recommendations here.

Summary Box

• Daily fixed-dose combination of ledipasvir (90 mg)/sofosbuvir (400 mg) with weight-based ribavirin for 12 weeks is a Recommended regimen for patients with HCV genotype 1 or 4 infection in the allograft, including those with compensated cirrhosis.
  Rating: Class I, Level A
   
• Daily daclatasvir (60 mg) plus sofosbuvir (400 mg) with low initial dose of ribavirin (600 mg, increased as tolerated) for 12 weeks is a Recommended regimen for patients with HCV genotype 1 or 4 infection in the allograft, including those with compensated cirrhosis.
  Rating: Class I, Level B

• Daily fixed-dose combination of ledipasvir (90 mg)/sofosbuvir (400 mg) for 24 weeks is a Recommended regimen for treatment-naïve patients with HCV genotype 1 or 4 infection in the allograft and with compensated liver disease, who are ribavirin ineligible.
  Rating: Class I, Level B
   
• Daily daclatasvir (60 mg) plus sofosbuvir (400 mg) for 24 weeks is a Recommended regimen for patients with HCV genotype 1 or 4 infection in the allograft and with compensated liver disease, who are ribavirin ineligible.
  Rating: Class II, Level C

• Daily fixed-dose combination of ledipasvir (90 mg)/sofosbuvir (400 mg) with low initial dose of ribavirin (600 mg, increased as tolerated) for 12 weeks is a Recommended regimen for liver-transplant recipients with decompensated cirrhosis (CTP class B or C) who have HCV genotype 1 or 4 infection in the allograft.
  Rating: Class I, Level B

• Daily simeprevir (150 mg) plus sofosbuvir (400 mg) with or without weight-based ribavirin for 12 weeks is an Alternative regimen for patients with HCV genotype 1 infection in the allograft, including those with compensated cirrhosis.
  Rating: Class I, Level B
   

• Daily fixed-dose combination of paritaprevir (150 mg)/ritonavir (100 mg)/ombitasvir (25 mg) plus twice-daily dosed dasabuvir (250 mg) with weight-based ribavirin for 24 weeks is an Alternative regimen for patients with HCV genotype 1 infection in the allograft, who have early-stage fibrosis (Metavir stage F0-F2).
  Rating: Class I, Level B

• Daily daclatasvir (60 mg) plus sofosbuvir (400 mg), with low initial dose of ribavirin (600 mg, increased as tolerated) for 12 weeks is a Recommended regimen for patients with HCV genotype 2 infection in the allograft, including those with compensated cirrhosis.
  Rating: Class II, Level A
   
• Daily sofosbuvir (400 mg) and weight-based ribavirin for 24 weeks is a Recommended regimen for patients with HCV genotype 2 infection in the allograft, including those with compensated cirrhosis.
  Rating: Class II, Level C

• Daily daclatasvir (60 mg) plus sofosbuvir (400 mg) for 24 weeks is a Recommended regimen for patients with HCV genotype 2 infection in the allograft, including those with with compensated cirrhosis, who are ribavirin ineligible.
  Rating: Class II, Level C

• Daily sofosbuvir (400 mg) and ribavirin (initial dose 600 mg/day, increased monthly by 200 mg/day as tolerated to weight-based dose) for 24 weeks is a Recommended regimen for liver-transplant recipients with decompensated cirrhosis (CTP class B or C) who have HCV genotype 2 infection in the allograft.
  Rating: Class II, Level C

• Daily daclatasvir (60 mg) plus sofosbuvir (400 mg) with low initial dose of ribavirin (600 mg, increased as tolerated) for 12 weeks is a Recommended regimen for patients with HCV genotype 3 infection in the allograft, including those with compensated cirrhosis.
  Rating: Class II, Level A

• Daily daclatasvir (60 mg) plus sofosbuvir (400 mg) for 24 weeks is a Recommended regimen for patients with HCV genotype 3 infection in the allograft, including those with compensated cirrhosis, who are ribavirin ineligible.
  Rating: Class II, Level C

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